The objective of this proposal is to analyze the mechanism that induces antigen-sensitive precursor cells to mature to antibody-forming cells. The physiological inductive stimulus requires the interaction of antigen and cooperating cell types with precursor cells. I utilize here the immunologic activities of bacterial lipopolysaccharides (LPS) as a probe to study the inductive stimulus. LPS, under defined conditions, induces precursor cells to mature to antibody-forming cells in the absence of antigen and cooperating cells. A strain of mice, CH3/HeJ has a single gene defect that limits the mitogenic and polyclonal response of precursor cells to LPS. Also in CH3/HeJ mice, this gene defect limits the ability of LPS to inhibit tolerance induction to deaggregated human gamma globulin. These immunologic activities of LPS will be correlated to the physiological role of cooperating cell types in the inductive stimulus. I will determine whether LPS will stimulate immune responses to an antigen (collagen) in strain of mice where thymus-derived cell activity is restricted by the immune response genes in the H-2 histocompatibility complex. LPS will be used to investigate the biochemical control of the inductive pathway in precursor cells. LPS induces selective changes in intracellular levels of cyclic nucleotides. The possible role of these cyclic nucleotides as intracellular mediators of signals delivered at cell surface membranes will be considered. Agents that exert selective effects on intracellular cyclic nucleotide metabolism may also affect the expression of the inductive pathway.